Molecular Genetics and Metabolism Reports最新文献

{"title":"OTC gene duplication as the possible cause of massive hyperammonaemia with a fatal prognosis","authors":"Borkowska Natalia ,&nbsp;Kaluzny Lukasz ,&nbsp;Rokicki Dariusz ,&nbsp;Szmida Elzbieta ,&nbsp;Kowalski Pawel ,&nbsp;Dus-Zuchowska Monika ,&nbsp;Skiba Pawel ,&nbsp;Ciara Elzbieta ,&nbsp;Biela Mateusz ,&nbsp;Rydzanicz Malgorzata ,&nbsp;Ploski Rafal ,&nbsp;Smigiel Robert","doi":"10.1016/j.ymgmr.2024.101146","DOIUrl":"10.1016/j.ymgmr.2024.101146","url":null,"abstract":"<div><div>Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder. It may occur due to various changes to the <em>OTC</em> gene located on the X chromosome. Many sequence variants in the <em>OTC</em> gene result in different severity and require different types of molecular testing. We present a familial case of hyperammonemia possibly caused by the small CNV (duplication) within exon 2 of the <em>OTC</em> gene that was not detected by standard sequencing methods. In this case, the knowledge of the underlying molecular changes to the gene results in an appropriate approach to future sibling screening. Collecting more data, especially regarding rare variants of genetic disorders, is essential as it will help to create the best diagnostic-therapeutic path in prenatal and neonatal care in the future. Early diagnosis and treatment can lead to a better prognosis, and this case emphasizes the importance of understanding genetic changes in OTC deficiency.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101146"},"PeriodicalIF":1.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142357435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rare case of fructose-1, 6-bisphosphatase deficiency: Clinical features in a pediatric patient","authors":"Shami Pokhrel,&nbsp;Subha Sainju,&nbsp;Prasanna Lamsal,&nbsp;Uma Devi Chhetri","doi":"10.1016/j.ymgmr.2024.101143","DOIUrl":"10.1016/j.ymgmr.2024.101143","url":null,"abstract":"<div><div>Fructose-1, 6- bisphosphatase deficiency is a rare autosomal recessive inborn error of fructose metabolism which mainly affects gluconeogenesis. It often presents with ketotic hypoglycemia and lactic acidosis, with hyperventilation. The disease has a high mortality rate when undiagnosed.</div><div>Here we report a case of this rare disorder, referred to our hospital in Western Nepal, diagnosed originally as pneumonia. The patient presented in respiratory distress with severe metabolic acidosis and dehydration. She also demonstrated hypoglycemia, hypernatremia, coagulation dysfunction and albuminuria, all of which gradually improved, though her lactate remained consistently elevated. This led to investigation of urinary ketones which were positive suggesting a defect in the metabolism of carbohydrates. Urine organic acid profile and whole exome sequencing finally confirmed the diagnosis of Fructose-1, 6- bisphosphatase deficiency. To our knowledge this is the first case report of this disease diagnosed in Nepal.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101143"},"PeriodicalIF":1.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MADD-like pattern of acylcarnitines associated with sertraline use","authors":"Filippo Ingoglia ,&nbsp;Mohsen Tanfous ,&nbsp;Benjamin Ellezam ,&nbsp;Katherine J. Anderson ,&nbsp;Marzia Pasquali ,&nbsp;Lorenzo D. Botto","doi":"10.1016/j.ymgmr.2024.101142","DOIUrl":"10.1016/j.ymgmr.2024.101142","url":null,"abstract":"<div><p>Multiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three groups: neonatal onset with congenital anomalies (type 1), neonatal onset without congenital anomalies (type 2), and attenuated and/or later onset (type 3). Here, we present two cases with biochemical profiles mimicking late-onset MADD but negative genetic testing, associated with the use of sertraline, a commonly used antidepressant. Case 1 is a 22 yo woman diagnosed with depression and profound fatigue who was referred to the metabolic clinic because of carnitine deficiency and a plasma acylcarnitine profile with a MADD-like pattern. Case 2 is a 61 yo woman with a history of chronic fatigue who was admitted to the emergency department with difficulty swallowing, metabolic acidosis, and mild rhabdomyolysis. Plasma acylcarnitine profile showed a MADD-like pattern. The muscle biopsy revealed lipid droplet accumulation and proliferation of mitochondria with abnormal osmiophilic inclusions, and a biochemical assay of the respiratory chain showed a deficit in complex II activity. In both cases, urine organic acid profile was normal, and genetic tests did not detect variants in the genes involved in MADD. Sertraline was on their list of medications and considering its association with inhibition of mitochondrial function and rhabdomyolysis, the team recommended the discontinuation under medical supervision. In Case 1 after discontinuation, the plasma acylcarnitine test normalized, only to return abnormal when the patient resumed sertraline. In Case 2, after sertraline was discontinued rhabdomyolysis resolved, and the muscle biopsy and biochemical assay of the respiratory chain normalized. Although sertraline is considered a safe drug, these two cases suggest that the use of sertraline may be associated with a potentially reversible form of mitochondrial dysfunction mimicking MADD. Further studies are needed to confirm and estimate the risk of MADD-like presentations with the use of sertraline, as well as identifying additional contributing factors, including genetic factors. Metabolic physicians should consider sertraline use in the differential diagnosis of MADD, particularly when genetic testing is negative.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101142"},"PeriodicalIF":1.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000958/pdfft?md5=5fe038506b2728ec375355d46e97c8be&pid=1-s2.0-S2214426924000958-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing clinical outcomes: The journey of twins with CRIM-negative infantile-onset Pompe disease on high-dose enzyme replacement therapy and immunomodulation","authors":"Angie H. Fares ,&nbsp;Ankit K. Desai ,&nbsp;Laura E. Case ,&nbsp;Cassie Sharon ,&nbsp;Amy Klinepeter ,&nbsp;Amelia Kirby ,&nbsp;Matthew T. Lisi ,&nbsp;Rebecca L. Koch ,&nbsp;Priya S. Kishnani","doi":"10.1016/j.ymgmr.2024.101141","DOIUrl":"10.1016/j.ymgmr.2024.101141","url":null,"abstract":"<div><p>Infantile-onset Pompe disease (IOPD) is caused by a deficiency in the enzyme acid alpha-glucosidase (GAA). It is characterized by severe and progressive hypertrophic cardiomyopathy and muscle weakness with death in the first 2 years of life if left untreated. Enzyme replacement therapy (ERT) with alglucosidase-alfa is lifesaving, but its effectiveness is influenced by the patient's cross-reactive immunologic material (CRIM) status, dose of ERT, and the development of high antibody titers, which can reduce the therapy's efficacy. The inability of CRIM-negative IOPD patients to produce native GAA exposes them to a high risk of development of anti-rhGAA IgG antibody titers, leading to treatment failure. We present the case of CRIM-negative dizygotic twins treated with high-dose alglucosidase-alfa (40 mg/kg/week), initiated at 28 days (Twin A) and 44 days (Twin B). Both twins received immune tolerance induction (ITI) with rituximab, methotrexate, and IVIG to mitigate antibody response. Initial evaluations revealed elevated left ventricular mass index (LVMI) and elevated biomarkers (urine glucose tetrasaccharide (Glc₄), creatine kinase (CK), and aspartate aminotransferase (AST)) in both twins. Following treatment, cardiac function and biomarkers normalized within several months, with a slight delay in Twin B compared to Twin A, likely attributed to the later initiation of ERT. Both twins safely tolerated ITI, achieving immune tolerance with low antibody titers. At 28 months, the twins transitioned to avalglucosidase-alfa (40 mg/kg every other week (EOW)), which was well tolerated without an increase in antibody titers. At 39 months, both twins exhibited normal cardiac function, LVMI, and biomarkers. Motor skills continued to improve, though some kinematic concerns persisted. These cases underscore the importance of early, high-dose ERT combined with ITI in managing CRIM-negative IOPD. While transitioning to avalglucosidase-alfa at 40 mg/kg/EOW was beneficial and well-tolerated in our patients, further studies are needed to confirm its long-term efficacy compared to the high-dose weekly 40 mg/kg alglucosidase-alfa.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101141"},"PeriodicalIF":1.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000946/pdfft?md5=9cd264e8af73cca2574ef0de8bc668a6&pid=1-s2.0-S2214426924000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Missense variants of FBN2 associated with congenital arachnodactyly in three Chinese families","authors":"Yu Sui,&nbsp;Yongping Lu,&nbsp;Meina Lin,&nbsp;Xinren Chen,&nbsp;Xiang Ni,&nbsp;Huan Li,&nbsp;Miao Jiang","doi":"10.1016/j.ymgmr.2024.101140","DOIUrl":"10.1016/j.ymgmr.2024.101140","url":null,"abstract":"<div><h3>Background</h3><p>Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder caused by pathogenic variants of Fibrillin-2 (<em>FBN2</em>) gene. This study aimed to investigate the variants in three Chinese families with CCA.</p></div><div><h3>Methods</h3><p>Next-generation sequencing analysis and Sanger sequencing of exons 24–35 of <em>FBN2</em> (NM_001999.4) were performed on the three CCA pedigrees. The pathogenicity of the variants was assessed using ACMG criteria and predicted using an in-silico program.</p></div><div><h3>Results</h3><p>A novel heterozygous substitution (NM_001999.4: c.3230G &gt; A; NP_001990.2 p. Cys1077Tyr) was identified in all patients from pedigree A, but not in healthy family members. The variant was found to be pathogenic. Additionally, in pedigree B (NM_001999.4: c.4222G &gt; A; NP_001990.2: p.Asp1408Asn) and C (NM_001999.4: c.3170G &gt; A; NP_001990.2: p.Gly1057Asp), and the previously reported variants were detected. Variants affecting cysteine residues may disrupt disulfide bridging, leading to a weakened microfibril scaffold, resulting in CCA phenotypes. High phenotypic heterogeneity was observed among different families, and there was little correlation between the genotype and phenotype.</p></div><div><h3>Conclusion</h3><p>This study describes three large families with CCA caused by missense variants in the <em>FBN2</em> gene. Phenotypic variations were observed among different pedigree groups, and further research is needed to investigate the underlying reasons for these variations.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101140"},"PeriodicalIF":1.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000934/pdfft?md5=65ae1d4fa45d800bf053f549131f8b0e&pid=1-s2.0-S2214426924000934-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An acute life-threatening episode of rhabdomyolysis, renal failure, altered mental status and hyperammonemia in an adult with 3-methylcrotonyl-CoA carboxylase deficiency","authors":"Rachel McGowan,&nbsp;Shoji Yano","doi":"10.1016/j.ymgmr.2024.101138","DOIUrl":"10.1016/j.ymgmr.2024.101138","url":null,"abstract":"<div><p>3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is an autosomal recessive disorder of leucine metabolism. Since 3-MCC deficiency is thought to be a benign condition, a few newborn screening programs discontinued to screen this condition. We report a case of a 24-year-old previously healthy male patient who developed generalized rhabdomyolysis, weakness, respiratory and renal failure, acute pancreatitis, hyperammonemia, and altered consciousness after strenuous exercise. Diagnosis of 3-MCC was made based on increased plasma C5OH carnitine, urine 3-methylcrotonylglycine, and 3-hydroxyisovalerate, and later whole genome sequencing study confirmed the diagnosis. Low plasma carnitine and high creatine kinase (CK) levels were again noted after two months of poor compliance with carnitine therapy. Since 3-MCC deficiency is often incidentally diagnosed in asymptomatic mothers through positive newborn screening in the newborns and most positive newborn screening cases have benign clinical outcomes, 3-MCC deficiency has been considered a benign condition. Observation of a life-threatening episode triggered by strenuous exercise and recurrent occurrence of low carnitine and high CK without carnitine supplementation may support 3-MCC deficiency to be the condition covered by the newborn screen since carnitine supplementation likely prevents an episode that can be life-threatening. Asymptomatic adults with 3-MCC deficiency may benefit from periodic evaluation of plasma carnitine levels.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101138"},"PeriodicalIF":1.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000910/pdfft?md5=8ec486bf2809c93573f13aafc0119a1e&pid=1-s2.0-S2214426924000910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid genotyping of inversion variants in Mucopolysaccharidosis type II using long-range PCR: A case report","authors":"Yusuke Hattori ,&nbsp;Jun Kido ,&nbsp;Keishin Sugawara ,&nbsp;Takaaki Sawada ,&nbsp;Shirou Matsumoto ,&nbsp;Kimitoshi Nakamura","doi":"10.1016/j.ymgmr.2024.101139","DOIUrl":"10.1016/j.ymgmr.2024.101139","url":null,"abstract":"<div><p>Mucopolysaccharidosis II (MPS II) is a lysosomal storage disease caused by a deficiency in iduronate-2-sulfatase (IDS), leading to the accumulation of dermatan sulfate and heparan sulfate in lysosomes. Traditionally, genotyping of the <em>IDS</em> gene has been conducted through exome sequencing, which fails to detect inversion variants. Consequently, when no pathogenic variants are detected in exons, additional PCR-based analysis is required. Herein, we introduce a rapid genotyping technique method using long-range PCR for MPS II patients. We successfully identified an inversion variant and confirmed the sequences of the inversion regions. We also confirmed that the pathogenic variant in the patient originated <em>de novo</em>. These findings suggest that long-range PCR genotyping can identify inversion variants more rapidly compared to the previous PCR-based methods, making it a valuable tool for newborn screening (NBS) and genetic diagnosis.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101139"},"PeriodicalIF":1.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000922/pdfft?md5=bb80a5595957f992b474ea8d2a3ed1a6&pid=1-s2.0-S2214426924000922-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ataluren-mediated nonsense variant readthrough in D-bifunctional protein deficiency: A case report","authors":"Rai-Hseng Hsu ,&nbsp;Ni-Chung Lee ,&nbsp;Hui-An Chen ,&nbsp;Wuh-Liang Hwu ,&nbsp;Wang-Tso Lee ,&nbsp;Yin-Hsiu Chien","doi":"10.1016/j.ymgmr.2024.101137","DOIUrl":"10.1016/j.ymgmr.2024.101137","url":null,"abstract":"<div><p>D-bifunctional protein (DBP) deficiency, a fatal peroxisomal enzyme disorder, typically manifests with life-threatening symptoms in the first two years of childhood. We present the case of an infant with elevated lysophosphatidylcholine C26:0 (C26:0-LPC) levels identified during X-linked adrenoleukodystrophy (ALD) screening, leading to a diagnosis of DBP deficiency due to a homozygous <em>HSD17B4</em> c.1041T&gt;A, p.(Tyr347Ter) variant. Starting at two months of age, the infant experienced seizures, hypotonia, and developmental delays, prompting the initiation of experimental treatment with the readthrough agent PTC124 (ataluren) at six months. The treatment led to a decrease in C26:0-LPC levels from 0.65 μM to 0.53 μM; concomitant fish oil supplementation transiently increased C26:0-LPC to 0.74 μM before returning to 0.53 μM after cessation of supplementation. The patient demonstrated improved swallowing and progressive motor and speech development during a two-year treatment period, with no further seizures. This case report highlights the potential of nonsense readthrough therapy for peroxisomal disorders, a group of metabolic diseases that currently lack targeted treatments.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101137"},"PeriodicalIF":1.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000909/pdfft?md5=3b87bdeb125a1aee0c39640f61ae6f15&pid=1-s2.0-S2214426924000909-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrafamilial phenotypic variability due to a missense pathogenic variant in FBP1 gene","authors":"Setila Dalili ,&nbsp;Nasrin Sedighi Pirsaraei ,&nbsp;Ameneh Sharifi ,&nbsp;Alireza Pouryousef ,&nbsp;Fatemeh Aghaee ,&nbsp;Reza Bayat ,&nbsp;Babak Ghavami ,&nbsp;Bahareh Rabbani ,&nbsp;Nejat Mahdieh","doi":"10.1016/j.ymgmr.2024.101136","DOIUrl":"10.1016/j.ymgmr.2024.101136","url":null,"abstract":"<div><h3>Background</h3><p>FBPase deficiency as an autosomal recessive disorder is due pathogenic variants in the FBP1 gene. It usually presents with hyperlactic acidemia and hypoglycaemia starting from early childhood. Here, genotypes and phenotypes of all reported patients and their distributions are presented. In addition, we present an Iranian family with two affected children presenting with unusual symptoms due to pathogenic variants in the <em>FBP1</em> gene.</p><p>Clinical evaluations and laboratory assessments were performed for the affected members. Whole exome sequencing (WES) was applied in order to find the causal variant. In addition to segregation analysis within the family, variant pathogenicity analyses and predictions were done via bioinformatics tools and according to ACMG guidelines. The genotypes and detailed clinical features were documented for all patients.</p></div><div><h3>Results</h3><p>The study included a population of 104 patients with different variants of the <em>FBP1</em> gene; 75 were homozygotes. The average age of onset was 14.97 months. The most frequent clinical features were metabolic acidosis (71 cases), hypoglycemia (70 cases), vomiting (46 cases), hyperuricemia (37 cases), and respiratory distress (25 cases). 74 families were from Asia. The most common genotypes were c.841G &gt; A/c.841G &gt; A and c.472C &gt; T/c.472C &gt; T. WES test showed a pathogenic homozygous variant, c.472C &gt; T in two cases of a family: a six-and-a-half-year-old girl with an older brother with different symptoms. All laboratory evaluations in the patient were normal except for the blood sugar. The patient experienced her first hypoglycemic episode at age 3.</p></div><div><h3>Conclusions</h3><p>This is an unusual presentation of FBPase deficiency with intrafamilial phenotypic variability.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101136"},"PeriodicalIF":1.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000892/pdfft?md5=40503765e68ec1c2af9b7684c24b3780&pid=1-s2.0-S2214426924000892-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The broad spectrum of clinical manifestations observed in three patients with L2 hydroxyglutaric aciduria spans from febrile seizures to complex dystonia","authors":"A. Alsayed ,&nbsp;M. Albadrani ,&nbsp;A. Obaid ,&nbsp;A. Alhashim ,&nbsp;A. Alakkas","doi":"10.1016/j.ymgmr.2024.101135","DOIUrl":"10.1016/j.ymgmr.2024.101135","url":null,"abstract":"<div><p>L-2 hydroxyglutaric aciduria (L-2-HGA) is a rare autosomal recessive progressive, organic aciduria which presents with a wide variety of clinical manifestations. Diagnosis is complex and necessitates an increase in clinical suspicion of the disease to obtain the necessary diagnostic tests and thus early administration of appropriate management.</p><p>In this case series, we are reporting three cases of patients with L-2-HGA who presented with a variety of clinical manifestations. All patients presented with a constellation of symptoms including febrile seizures, hyperactivity and intellectual difficulties. One case had an unusual presentation of cervical dystonia in early adulthood. Another case had a homozygous variant, <em>L2HGDH</em>: NM_024884.3: c.368 A &gt; G p. (Tyr123Cys) classified as variant of uncertain significance (VUS) at that time but recently has been reclassified as likely pathogenic variant in clin var. Furthermore, brain MRI of two patients depicted characteristic signs consistent with L-2-HGA. The findings include, symmetrical confluent high T2/FLAIR signal intensity of the white matter involving the subcortical U fibers and deep white matter with sparing of the immediate periventricular white matter, internal capsules and corpus callosum. There was also symmetric abnormal T2 signal intensity of the caudate nuclei, lentiform nucleus as well as the dentate nuclei of the cerebellum.</p><p>Overall, only few cases with similar genetic mutation have been documented in the literature and were of Saudi origin. The aim of the study is to highlight the clinico-radiological features of L-2-HGA to aid in early, prompt diagnosis, and thus appropriate follow up and management of the disease with riboflavin, levocarnitine and a low-lysine diet.</p></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"41 ","pages":"Article 101135"},"PeriodicalIF":1.8,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214426924000880/pdfft?md5=a48dd86bc822e285d3adf2139d2730f6&pid=1-s2.0-S2214426924000880-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142050445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}